Tag: retrovirus

The copied gene that gave dachshunds and corgis their short legs

By Ed Yong | July 16, 2009 1:00 pm

Blogging on Peer-Reviewed ResearchCompare the elegant grace of a running wolf with the comical shuffle of a waddling dachshund, and you begin to understand what millennia of domestication and artificial selection can do to an animal. As dachshunds develop, the growing tips of their limb bones harden early, stunting their growth and leading to a type of dwarfism called chondrodysplasia. The same applies to at least 19 modern breeds including corgis, Pekingese and basset hounds, all of which have very short, curved legs.

Dachshund.jpgThese breeds highlight the domestic dog’s status as the most physically diverse of mammals. Now, a team of scientists led by Heidi Parker from the National Human Genome Research Institute have found the genetic culprit behind the stumpy limbs of all these breeds, and its one with surprising relevance for dwarfism in humans. 

All cases of stunted legs in domestic dogs are the result of a single genetic event that took place early on in their evolution. Some time ago, a gene called FGF4 (short for fibroblast growth factor 4), which plays an important role in bone growth, was copied and reinserted into a new site in the dog genome. It’s this extra errant copy – a retrogene – that has retarded the growth of so many domestic breeds.

Parker’s team sequenced genes from over 835 dogs across 76 different breeds, including 95 short-legged individuals, and found a genetic signature unique to these stunted animals. This included a handful of genetic variants – each consisting of a single altered base pair or “DNA letter” – that were overrepresented in the short-legged breeds and that clustered in the same site. One of these variants was 30 times more common in the short-legged breeds than their long-limbed peers.

The team found that this mystery region exactly matched a gene called fibroblast growth factor (FGF4). That was puzzling, for FGF4 normally sits at a very different location, some distance away on the dog genome. In fact, Parker found that the short-legged breeds have two copies and the one associated with their abnormal growth has been inserted in an unusual site. Not only did all the stunted animals have this errant FGF4 gene, but 96% of them had two identical copies of it.

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Resistance to an extinct virus makes us more vulnerable to HIV

By Ed Yong | May 9, 2009 12:00 pm

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Immunity to viral infections sounds like a good thing, but it can come at a price. Millions of years ago, we evolved resistance to a virus that plagued other primates. Today, that virus is extinct, but our resistance to it may be making us more vulnerable to the present threat of HIV.

Our resistance to the ancient PtERV1 may explain our vulnerability to HIV.Many extinct viruses are not completely gone. Some members of a group called retroviruses insinuated themselves into our DNA and became a part of our genetic code. Indeed, a large proportion of the genomes of all primates consists of the embedded remnants of ancient viruses. Looking at these remnants is like genetic archaeology, and it can tell us about infections both past and present.

When retroviruses (such as HIV, right) infect a cell, they insert their own DNA into their host’s genome, using it as a base of operations. From there, the virus can pop out again and make new copies of itself, re-infect its host or move on to new cells.

If it manages to infect an egg or sperm cell, the virus could pass onto the next generation. Hidden inside the embryo’s DNA, it becomes replicated trillions of times over and ends up in every single one of the new individual’s cells.

These hitchhikers are called ‘endogenous retroviruses‘. While they could pop out at any time, they quickly gain mutations in their DNA that knocks out their ability to infect. Unable to move on, they become as much a part of the host’s DNA as its own genes.

In 2005, a group of scientists led by Evan Eichler compared endogenous retroviruses in different primates and found startling differences. In particular, chimps and gorillas have over a hundred copies of the virus PtERV1 (or Pan troglodytes endogenous retrovirus in full). Our DNA has none at all, and this is one of the largest differences between our genome and that of chimps.

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